| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
- Kulmala, J., et al.
(författare)
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Association between mid- to late life physical fitness and dementia : evidence from the CAIDE study
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 276:3, s. 296-307
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. This study investigated the association between perceived physical fitness at midlife, changes in perceived fitness during the three decades from mid-to late life and dementia risk. Design. Prospective cohort study. Setting. Cardiovascular risk factors, ageing and incidence of dementia (CAIDE) study. Subjects. Subjects were selected from four independent, random samples of population-based cardiovascular surveys and were first examined in 1972, 1977, 1982 or 1987, when they were on average 50 years old. The CAIDE target population included 3559 individuals. A random sample of 2000 individuals still alive in 1997 was drawn for re-examinations (performed in 1998 and 2005-2008) that consisted of cognitive assessments, with 1511 subjects participating in at least one re-examination. Dementia diagnoses were also confirmed from national registers for the entire target population. Main outcome measure. All-cause dementia. Results. Poor physical fitness at midlife was associated with increased dementia risk in the entire target population [hazard ratio (HR), 1.5; 95% confidence interval (CI), 1.1-2.0]. In participants, odds ratio (OR) was 2.0 (95% CI, 0.9-4.0). This association was significant in apolipoprotein E epsilon 4 allele (APO epsilon 4) noncarriers (OR, 4.3; 95% CI, 1.4-13.3), men (HR, 1.8; 95% CI, 1.1-3.0) and people with chronic conditions (HR, 2.9; 95% CI, 1.3-6.6). A decline in fitness after midlife was also associated with dementia (OR, 3.0; 95% CI, 1.7-5.1), which was significant amongst both men and women and more pronounced in APOE epsilon 4 carriers (OR, 4.4; 95% CI, 2.1-9.1). Conclusions. Perceived poor physical fitness reflects a combination of biological and lifestyle-related factors that can increase dementia risk. A simple question about perceived physical fitness may reveal at-risk individuals who could benefit from preventive interventions.
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| 3. |
- Sindi, S., et al.
(författare)
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Baseline telomere length and effects of a multidomain lifestyle intervention on cognition : The FINGER randomized controlled trial
- 2017
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 59:4, s. 1459-1470
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte telomere length (LTL) is a biomarker of aging, and it is associated with lifestyle. It is currently unknown whether LTL is associated with the response to lifestyle interventions. The goal is to assess whether baseline LTL modified the cognitive benefits of a 2-year multidomain lifestyle intervention (exploratory analyses). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a 2-year randomized controlled trial including 1,260 people at risk of cognitive decline, aged 60-77 years identified from the general population. Participants were randomly assigned to the lifestyle intervention (diet, exercise, cognitive training, and vascular risk management) and control (general health advice) groups. Primary outcome was change in cognition (comprehensive neuropsychological test battery). Secondary outcomes were changes in cognitive domains: Memory, executive functioning, and processing speed. 775 participants (392 control, 383 intervention) had baseline LTL (peripheral blood DNA). Mixed effects regression models with maximum likelihood estimation were used to analyze change in cognition as a function of randomization group, time, baseline LTL, and their interaction. Intervention and control groups did not significantly differ at baseline. Shorter LTL was related to less healthy baseline lifestyle. Intervention benefits on executive functioning were more pronounced among those with shorter baseline LTL (p-value for interaction was 0.010 adjusted for age and sex, and 0.007 additionally adjusted for baseline lifestyle factors). The FINGER intervention cognitive benefits were more pronounced with shorter baseline LTL, particularly for executive functioning, indicating that the multidomain lifestyle intervention was especially beneficial among higher-risk individuals.
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| 4. |
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| 5. |
- Sindi, S., et al.
(författare)
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Midlife improvements in financial situation are associated with a reduced dementia risk later in life : the CAIDE 30-year study
- 2020
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 32:11, s. 1317-1324
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Perceived financial strain is associated with various health conditions, but it is unknown whether it is associated with an increased risk for dementia. The goal is to examine the associations between midlife perceptions of financial situation and dementia risk later in life.Methods: Participants were derived from the Cardiovascular Risk Factors, Aging, and Dementia population-based cohort study (n = 2000) (between 1972 and 1987, baseline mean age 50 years) in Finland. Participants returned for two re-examinations in late life (in 1998 and 2005–2008, mean age 71 and 78 years). In this study, 1442 subjects that participated in at least one re-examination (mean total follow-up 25 years) were included in analyses. Financial strain was measured using two questions in midlife on perceptions of financial situation and perceptions of changes in financial situation. For each question, participants were categorized into three groups reporting improvement, worsening, or stability, with the latter set as the reference group. Analyses were adjusted for potential confounding factors.Results: The group reporting better financial situation had a reduced risk for dementia (fully adjusted model: odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33–0.86). In contrast, the group reporting worse financial situation did not have an increased risk for dementia (OR: 1.04, 95% CI: 0.53–2.02). Analyses on perceptions of current financial situation showed that the groups reporting satisfaction or dissatisfaction with financial situation did not differ in risk for dementia.Conclusion: This study is the first to show that midlife improvements in financial situation are associated with a reduced dementia risk later in life. Potential pathways related to stress reduction, improved lifestyle, and potential biological mechanisms are discussed.
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| 6. |
- Sindi, S., et al.
(författare)
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Sleep disturbances and dementia risk: A multicenter study
- 2018
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:10, s. 1235-1242
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk. Methods: Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project [Sweden]; Cardiovascular Risk Factors, Aging and Dementia study [Finland]). Late-life baseline analyses (3-10 years follow-up) used all three studies (N = 1446). Baseline ages 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and approximate to 84 years (Kungsholmen Project). Midlife baseline (age approximate to 50 years) analyses used Cardiovascular Risk Factors, Aging and Dementia (21 and 32 years follow-up) (N = 1407). Results: Midlife insomnia (fully adjusted hazard ratio = 1.24, 95% confidence interval = 1.02-1.50) and late-life terminal insomnia (fully adjusted odds ratio = 1.94, 95% confidence interval = 1.08-3.49) were associated with a higher dementia risk. Late-life long sleep duration (>9 hours) was also associated with an increased dementia risk (adjusted odds ratio = 3.98, 95% confidence interval = 1.87-8.48). Discussion: Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 7. |
- Sindi, S., et al.
(författare)
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Sleep disturbances and later cognitive status: a multi-centre study
- 2018
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Ingår i: Sleep Medicine. - : Elsevier BV. - 1389-9457 .- 1878-5506. ; 52:December, s. 26-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the associations between sleep disturbances in mid-life and late-life and late-life cognitive status. Methods: In four population-based studies (three Swedish studies: H70 study, Kungsholmen Project (KP) and The Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD); and one Finnish study: Cardiovascular Risk Factors, Aging and Dementia (CAIDE)), participants provided self-reports on insomnia, nightmares and general sleep problems. Late-life cognitive status was measured by the Mini Mental State Exam (MMSE). The associations between late-life sleep disturbances and cognition 3-11 years later were investigated across all studies (n = 3210). Mean baseline ages were 70 (CAIDE, H70 and SWEOLD), and 84 years (KP). Additional analyses examined the association between midlife sleep and late-life cognition using CAIDE (21 and 31 years follow-up, n = 1306, mean age 50 years), and SWEOLD (20-24 years follow-up, n = 2068, mean age 58 years). Ordered logistic regressions, adjusted for potential baseline confounders, were used in the analyses. Results: Late-life sleep disturbances were associated with poorer cognition after 3-11 years (fully adjusted beta = -0.12, 95% CI = -0.24 to -0.01). Midlife nightmares and insomnia were also associated with lower MMSE scores (fully adjusted beta = -0.28, 95% CI = -0.49 to -0.07 and beta = -0.20, 95% CI = -0.39 to -0.01), although the latter association was attenuated after adjusting for lifestyle/health-related confounders. Midlife general sleep problems were not associated with late-life MMSE performance. Conclusions: Sleep disturbances and midlife nightmares were associated with lower MMSE scores, which suggests that sleep disturbances in earlier life stages can be associated with worse late-life cognition. (c) 2017 Published by Elsevier B.V.
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| 8. |
- Sindi, S., et al.
(författare)
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Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline : A Randomized Clinical Trial
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 76:3, s. 491-498
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs). METHODS: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989). RESULTS: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264). CONCLUSIONS: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits. CLINICAL TRIALS REGISTRATION NUMBER: NCT01041989.
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